Bolus injection of hypertonic solutions for cerebral edema in rats: challenge of homeostasis of healthy brain

Abstract

Hypertonic solutions are mainstay of osmotherapy to cerebral edema. How hypertonic solutions affect healthy brain homeostasis, however, is not fully understood. Using rat model of cerebral edema induced by local cryoinjury, we found with immunohistochemistry that less microglial activation in healthy hemishere 24 h after hypertonic saline (HS, 3% NaCl) administration, compared to mannitol (20%, the same osmotic concentration of 3% NaCl) while dehydrating the brain tissue. To see whether blood-brain barrier (BBB) or aquaporin-4 (AQP4) contribute to this difference, HS or mannitol was intra-arterially injected to normal rats, and BBB opening, ultrastructure and AQP4 immunoreactivity were examined. Evans blue extravasation indicated that BBB was opened much lighter in HS group than mannitol group at the same time points. Electron microscopy also showed edema around the capillaries slightly lighter in HS than mannitol group 24 h after injection. Meanwhile, HS injection led to AQP4 down regulation in expression similarly as mannitol, compared with NS group. These data suggested that bolus injection of hypertonic agents may lead to microglia activation in healthy brain in different extent, due to BBB compromise, instead of water movement or AQP4 expression. Hence in clinical application, BBB of healthy brain should be considered in perspective to maintain the brain homeostasis.